Glycogen, a naturally sourced highly branched polysaccharide nanoparticle, has been receiving attention in the field of nanomedicine due to its inherent non-toxicity and biodegradability. However, often in the literature glycogen nanoparticles (NPs) are used that come from different commercial sources (animals and tissues), which have significantly different sizes, molecular weights, and protein content, meaning a comprehensive overview of the interactions of these differently-sourced NPs with the human immune system is missing. Herein, we investigated coagulation, immune cell association and inflammation responses triggered by source-dependent interactions of glycogen NPs in human blood, utilising four types of commercially available glycogen: phytoglycogen (PG) isolated from sweet corn kernels, oyster glycogen (OG), rabbit liver glycogen (RLG), and bovine liver glycogen (BLG). Our results reveal that glycogen NPs exhibit minimal immune cell association, low complement factor, granulocyte, and platelet activation, and have no impact on blood clotting. This is despite the significant physico-chemical differences between the NP types, and when studied at exceptionally high particle concentrations (orders of magnitude higher than other typically studied synthetic systems). Given the similarities in the interactions with blood, either of the commercial glycogens can be leveraged in nanomedicine with respect to immuno-interactions, though PG provides a sustainable and ethically sourced form of NPs from plants. Together, our results highlight a key benefit of using glycogen NPs as injectable biomaterials for therapeutic applications.